A single-scan protocol for absolute D2/3 receptor quantification with [123I]IBZM SPECT

Purpose: Molecular imaging of the D2/3 receptor is widely used in neuropsychiatric research. Non‐displaceable binding potential (BPND) is a very popular quantitative index, defined as the product of the receptor concentration (Bavail) and the radiotracer affinity for the receptor (1/appKd). As the appKd is influenced by parameters such as the endogenous neurotransmitter dynamics, it often constitutes a confounding factor in research studies. A simplified method for absolute quantification of both these parameters would be of great interest in this context. Here, we describe the use of a partial saturation protocol that permits to produce an in vivo Scatchard plot and thus estimate Bavail and appKd separately, through a single dynamic SPECT session. To validate this approach, a multi‐injection protocol is used for the full kinetic modeling of [123I]IBZM using a 3‐tissue compartment, 7‐parameter model (3T‐7k). Finally, more “classic” BPND estimation methods are also validated against the results of the 3T‐7k. Methods: Twenty‐nine male rats were used. Binding parameters were estimated using the 3T‐7k in a multi‐injection protocol. A partial saturation protocol was applied at the region‐ and voxel‐level and results were compared to those obtained with the 3T‐7k model. The partial saturation protocol was applied after an adenovirus‐mediated D2 receptor striatal overexpression and in an amphetamine‐induced dopamine release paradigm. The Simplified Reference Tissue Model (SRTM), the Logan's non‐invasive graphical analysis (LNIGA) and a simple standardized uptake ratio (SUR) method were equally applied. Results: The partial saturation experiments gave similar values as the 3T‐7k both at the regional and voxel‐level. After adenoviral‐mediated D2‐receptor overexpression, an increase in Bavail by approximately 18% was observed in the striatum. After amphetamine administration, a 16.93% decrease in Bavail (p<0.05) and a 39.12% increase (p<0.01) in appKd was observed. BPND derived from SRTM, LNIGA and SUR correlated well with the Bavail values from the 3T‐7k (r=0.84, r=0.84 and r=0.83, respectively, p<0.0001 for all correlations). Conclusion: A partial saturation protocol permits the non‐invasive and time‐efficient estimation of Bavail and appKd separately. Given the different biological phenomena that underlie these parameters, this method may be applied for the in‐depth study of the dopaminergic system in translational molecular imaging studies. It can detect the biological variations in these parameters, dissociating the variations in receptor density (Bavail) from affinity (1/appKd), which reflects the interactions of the receptor with its endogenous ligand. HIGHLIGHTSResearch suggests dissociative changes in Bavail and appKd of neuroreceptors.Currently these parameters are jointly estimated as binding potential (BP).A single‐scan non‐invasive protocol for separate estimation is proposed.Sufficient sensitivity for biological studies is validated.Endogenous transmitter level assessed through appKd estimation.